Rationale. The gene therapy program is highly dependent upon the generation and maintenance of transgenic and hybrid transgenic mice for the study of cystic fibrosis and other diseases. This core is designed to take advantage of established expertise in the generation of the transgenic mice for the study of lung disease and in gene ablation studies that will be required for the present program projects. Likewise, maintenance of germ-free transgenic lines will be critical in supplying genotyped mice for the various projects. This core will both generate the new transgenic lines and gene targeted mice, as well as maintain breeding and genotype analysis for the transgenic mice already generated, as required for the individual projects and investigators. This Core will: 1) provide animal husbandry, breeding, tail clip, Southern blot, PCR analysis for the established lines necessary for the present application; 2) generate all new transgenic lines described in the protocols by pronuclear injection and gene targeting; 3) facilitate long term maintenance and surveillance of viral exposed animals required for the various projects. The animals will be maintained in sterile- barrier caging in a separate, germ-free facility at the Children's Hospital Research Foundation under the direction of Gary Keller, D.V.M. This program includes sentinel mice and careful ongoing surveillance and screening for other pathogens. This aspect of Core will interact closely with the Clinical Viral Core for vector safety issues. Such surveillance will be critical in the evaluation of lung disease in our various transgenic models and be necessary for the interpretation of genetic vs. environmental effects on lung injury or development.